The proposed studies will investigate the cellular mechanisms for carcinogenesis in human cells. For these studies we will use tissue cultures of cells derived from patients with the disease xeroderma pigmentosum, an inherited disease of DNA repair deficiency, predisposing to cancer. The goals of the study will be to identify the cellular mechanisms responsible for repair of the DNA. To accomplish this, we will transform xeroderma pigmentosum cells and then transfect such cells with DNA repair genes. There will be two basic approaches in the transfection experiments: one will be to transfect the cells with prokaryotic DNA repair genes, and the second will be to transfect the cells with isolated human DNA repair genes. We will use two basic approaches to identify the human genes: one will be to identify the human genes by complementation of the human DNA repair defect by use of other eukaryotic DNA repair genes, identification of such genes and their use to cross-hybridize and identify the human genes. Alternatively, we will isolate the human DNA repair proteins through a complementation assay, develop antibodies to these proteins, and use the antibody to enrich for mRNA encoding for the DNA repair genes which can then be identified.